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http://dx.doi.org/10.4014/jmb.1810.10062

Biosynthesis of Chondroitin in Engineered Corynebacterium glutamicum  

Cheng, Fangyu (Department of Chemical Engineering, Tsinghua University)
Luozhong, Sijin (Department of Chemical Engineering, Tsinghua University)
Yu, Huimin (Department of Chemical Engineering, Tsinghua University)
Guo, Zhigang (Department of Chemical Engineering, Tsinghua University)
Publication Information
Journal of Microbiology and Biotechnology / v.29, no.3, 2019 , pp. 392-400 More about this Journal
Abstract
Chondroitin, the precursor of chondroitin sulfate, which is an important polysaccharide, has drawn significant attention due to its applications in many fields. In the present study, a heterologous biosynthesis pathway of chondroitin was designed in a GRAS (generally recognized as safe) strain C. glutamicum. CgkfoC and CgkfoA genes with host codon preference were synthesized and driven by promoter Ptac, which was confirmed as a strong promoter via GFPuv reporter assessment. In a lactate dehydrogenase (ldh) deficient host, intracellular chondroitin titer increased from 0.25 to 0.88 g/l compared with that in a wild-type host. Moreover, precursor enhancement via overexpressing precursor synthesizing gene ugdA further improved chondroitin titers to 1.09 g/l. Chondroitin production reached 1.91 g/l with the engineered strain C. glutamicum ${\Delta}L-CgCAU$ in a 5-L fed-batch fermentation with a single distribution $M_w$ of 186 kDa. This work provides an alternative, safe and novel means of producing chondroitin for industrial applications.
Keywords
Chondroitin biosynthesis; engineered Corynebacterium glutamicum; lactate dehydrogenase deficient; precursor enhancement; fed-batch fermentation;
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